Our research program is broadly aimed at understanding the biochemistry and physiology of iron in an effort to improve iron in the human population: We are directing our activities toward the following goals: Synthesis and nutritional evaluation of efficacious iron supplements for specific therapeutic and prophylactic applications: New forms of chelated and polymeric ferric iron offer distinct advantages over ferrous sulfate and conventional food iron additives for oral iron therapy and iron fortification of foodstuffs. 2. Establishing the mechanisms of gastrointestinal iron absorption and its regulation: We are approaching the biochemistry of intestinal iron transport through better knowledge of the control and regulation of intestinal iron absorption. We are developing a hypothesis that the ability of the intestine to absorb and transport iron is determined not by body iron stores, but by the amount of nutritionally available iron to which the intestinal mucosa has become conditioned. 3. Understanding the mechanisms of iron storage: We are examining the properties of the iron storage protein, ferritin, in vivo and in vitro to increase our knowledge of the metabolism of excess iron. We hypothesize that copper affects ferritin either by binding to specific transition-metal binding sites or by its role in oxidative enzymes that induce post-transcriptional modifications of the protein. 4. Development of potential tests of iron assimilation in man: We are developing a new method utilizing the absorption and excretion of inorganic cobalt to measure relative biological availability of iron. This test shows promise as a non-radioactive technique for "probing" iron absorption in the human. We are investigating the origin and significance of serum ferritin in the rat to develop a rational basis for the use of serum ferritin immunoradiometric assay as a valid indicator of iron stores in the human.